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Cell Mar 2015One-fourth of all deaths in industrialized countries result from coronary heart disease. A century of research has revealed the essential causative agent:... (Review)
Review
One-fourth of all deaths in industrialized countries result from coronary heart disease. A century of research has revealed the essential causative agent: cholesterol-carrying low-density lipoprotein (LDL). LDL is controlled by specific receptors (LDLRs) in liver that remove it from blood. Mutations that eliminate LDLRs raise LDL and cause heart attacks in childhood, whereas mutations that raise LDLRs reduce LDL and diminish heart attacks. If we are to eliminate coronary disease, lowering LDL should be the primary goal. Effective means to achieve this goal are currently available. The key questions are: who to treat, when to treat, and how long to treat.
Topics: Animals; Cardiovascular Diseases; Cholesterol; Coronary Vessels; Dietary Fats; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Receptors, LDL
PubMed: 25815993
DOI: 10.1016/j.cell.2015.01.036 -
Journal of the American College of... Jun 2023
Topics: Humans; Plaque, Atherosclerotic; Atherosclerosis; Rupture, Spontaneous
PubMed: 37286251
DOI: 10.1016/j.jacc.2023.05.001 -
Redox Biology Aug 2017Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving... (Review)
Review
Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.
Topics: Angiogenesis Inhibitors; Animals; Clinical Trials as Topic; Disease Progression; Humans; Neovascularization, Pathologic; Oxidative Stress; Plaque, Atherosclerotic
PubMed: 28212521
DOI: 10.1016/j.redox.2017.01.007 -
Swiss Dental Journal 2017Rupture of an atherosclerotic plaque is the usual initiating event in an acute coronary syndrome (ACS). Persistent thrombotic occlusion at the site of plaque rupture...
Rupture of an atherosclerotic plaque is the usual initiating event in an acute coronary syndrome (ACS). Persistent thrombotic occlusion at the site of plaque rupture results in acute myocardial infarction. The early management of the patient is essential and crucially affects the prognosis of an ACS. Management includes the relief of ischemic pain and the initiation of an antithrombotic therapy, including an antiplatelet and anticoagulant therapy with aspirin and heparin to prevent further thrombosis of or embolism from an ulcerated plaque.
Topics: Acute Coronary Syndrome; Anticoagulants; Coronary Thrombosis; Drug Therapy, Combination; Early Medical Intervention; Humans; Myocardial Infarction; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Prognosis; Rupture, Spontaneous
PubMed: 28266687
DOI: 10.61872/sdj-2017-02-04 -
Theranostics 2024Smooth muscle cell (SMC) remodeling poses a critical feature in the development and progression of atherosclerosis. Although fate mapping and in silicon approaches have...
Smooth muscle cell (SMC) remodeling poses a critical feature in the development and progression of atherosclerosis. Although fate mapping and in silicon approaches have expanded SMC phenotypes in atherosclerosis, it still remains elusive about the contributions of individual SMC phenotypes and molecular dynamics to advanced atherosclerotic plaque. Using single-cell transcriptome, we investigated cellular compositions of human carotid plaque laden with atherosclerotic core, followed by in vivo experiments utilizing SMC-lineage tracing technology, bulk RNA sequencing (RNA-seq) and both in vivo and in vitro validation of the underlying molecular mechanism. 5 functionally distinct SMC subtypes were uncovered based on transcriptional features (described as contractile, fibroblast-like, osteogenic, synthetic and macrophage-like) within the niche. A proinflammatory, macrophage-like SMC subtype displaying an intermediary phenotype between SMC and macrophage, exhibits prominent potential in destabilizing plaque. At the molecular level, we explored cluster-specific master regulons by algorithm, and identified interferon regulatory factor-8 (IRF8) as a potential stimulator of SMC-to-macrophage transdifferentiation via activating nuclear factor-κB (NF-κB) signaling. Our study illustrates a comprehensive cell atlas and molecular landscape of advanced atherosclerotic lesion, which might renovate current understanding of SMC biology in atherosclerosis.
Topics: Humans; Plaque, Atherosclerotic; Atherosclerosis; Gene Expression Profiling; Myocytes, Smooth Muscle; Macrophages
PubMed: 38389849
DOI: 10.7150/thno.87201 -
The American Journal of Cardiology Oct 2023Acute coronary syndromes and, in particular, ST-elevation myocardial infarction are usually caused by coronary thrombosis in which the thrombus develops either on a... (Review)
Review
Acute coronary syndromes and, in particular, ST-elevation myocardial infarction are usually caused by coronary thrombosis in which the thrombus develops either on a disrupted plaque (usually a thin-capped fibroatheroma) or an eroded atherosclerotic plaque. These thrombus-prone plaques are vulnerable or high-risk. Although, traditionally, cardiologists have concentrated on treating significant coronary obstruction, there has been great interest over the last 2 decades in possibly preventing the thrombotic causes of myocardial infarction/sudden coronary death by mostly identifying and stabilizing these asymptomatic vulnerable or high-risk plaques, which, at least on invasive angiography, are mostly nonobstructive. Computed tomographic angiography and intravascular imaging during invasive coronary angiography have now been shown to identify a majority of these vulnerable or high-risk plaques before symptoms, thus opening up new preventive strategies. In conclusion, this article discusses the identification and management of these thrombus-prone lesions and patients with these lesions either with noninvasive techniques and systemic therapies or possibly through a new and bold interventional paradigm.
Topics: Humans; Plaque, Atherosclerotic; Coronary Thrombosis; Acute Coronary Syndrome; Cardiologists; Coronary Angiography
PubMed: 37611413
DOI: 10.1016/j.amjcard.2023.07.121 -
American Journal of Physiology. Cell... Feb 2024Despite years of study and major research advances over the past 50 years, atherosclerotic diseases continue to rank as the leading global cause of death. Accumulation... (Review)
Review
Despite years of study and major research advances over the past 50 years, atherosclerotic diseases continue to rank as the leading global cause of death. Accumulation of cholesterol within the vascular wall remains the main problem and represents one of the early steps in the development of atherosclerotic lesions. There is a complex relationship between vesicular cholesterol transport and atherosclerosis, and abnormalities in cholesterol trafficking can contribute to the development and progression of the lesions. The dysregulation of vesicular cholesterol transport and lysosomal function fosters the buildup of cholesterol within various intracytoplasmic compartments, including lysosomes and lipid droplets. This, in turn, promotes the hallmark formation of foam cells, a defining feature of early atherosclerosis. Multiple cellular processes, encompassing endocytosis, exocytosis, intracellular trafficking, and autophagy, play crucial roles in influencing foam cell formation and atherosclerotic plaque stability. In this review, we highlight recent advances in the understanding of the intricate mechanisms of vesicular cholesterol transport and its relationship with atherosclerosis and discuss the importance of understanding these mechanisms in developing strategies to prevent or treat this prevalent cardiovascular disease.
Topics: Humans; Atherosclerosis; Cholesterol; Plaque, Atherosclerotic; Foam Cells; Lysosomes
PubMed: 38145298
DOI: 10.1152/ajpcell.00415.2023 -
Journal of Atherosclerosis and... 2015Atherosclerosis is a progressive disease characterized by the accumulation of lipids in medium to large sized arteries. Atherothrombosis is a term used to describe... (Review)
Review
Atherosclerosis is a progressive disease characterized by the accumulation of lipids in medium to large sized arteries. Atherothrombosis is a term used to describe formation of a thrombus after rupture of an atherosclerotic plaque. Thrombosis can lead to myocardial infarction and stroke. Risk factors for atherosclerosis include hyperlipidemia, diabetes, smoking and hypertension all of which increase tissue factor (TF) expression. High levels of TF are present in atherosclerotic plaques due to expression by macrophages and vascular smooth muscle cells and the presence of cell-derived TF-positive microvesicles (MVs). In addition, hyperlipidemia leads to the formation of oxidized LDL, which induces TF expression in circulating monocytes and the release of TF-positive MVs. The major source of TF that drives thrombosis after plaque rupture is TF within the plaque. However, TF in the blood on monocytes and MVs may also contribute the thrombosis. Inhibition of the TF/factor VIIa complex is unlikely to be an effective strategy to reduce atherothrombosis due the essential role of the complex in hemostasis. However, selective blockade of pathologic TF without affecting protective TF may be effective in reducing atherothrombosis. For instance, statins have been shown to reduce TF expression in the plaque and in circulating monocytes, which would be expected to reduce thrombosis. Further studies are needed to determine safe strategies to reduce pathologic TF expression and atherothrombosis.
Topics: Animals; Humans; Plaque, Atherosclerotic; Thromboplastin; Thrombosis
PubMed: 26016513
DOI: 10.5551/jat.30940 -
Journal of the American College of... Mar 2020
Topics: Humans; Lipids; Plaque, Atherosclerotic; Stents
PubMed: 32216906
DOI: 10.1016/j.jacc.2020.01.043 -
European Heart Journal Nov 2020
Topics: Coronary Thrombosis; Humans; Plaque, Atherosclerotic
PubMed: 33174607
DOI: 10.1093/eurheartj/ehaa831